Evidence exists to suggest that the intestinal mucosal barrier to potentially harmful macromolecules (bacterial toxins and food antigens) is inadequate (1,2). The intestinal epithelial surface undergoes profound morphologic and physiologic changes during weaning in order to adapt to a new diet (3). These changes could result in the alteration of membrane surface characteristics which affect the attachment and uptake of macromolecules. A comprehensive study on the developmental changes in composition, organization and function of intestinal microvillus surface from immature animals may contribute to our overall knowledge of intestinal mucosal barrier function. The primary objective of this proposal is therefore to characterize the compositional and organizational changes in microvillus membrane (MVM), from suckling, weaning and postweaned rats and to determine if these developmental changes correspond with the development of mucosal barrier function. MVM surface will be characterized by lectins, cholera toxin and Ca++ binding. The organizational changes in MVM will be investigated by electron spin resonance with fatty acid and protein specific spin labels. The composition of MVM will be analyzed as to the lipid to protein ratio and lipid components (phospholipids, cholesterol, glycolipids and fatty acids). The functional capacity of the epithelial surface will be assessed by the binding of macromolecules (IgG, Beta-lactoglobulin, bovine serum albumin and E. coli endotoxin) to MVM. Results from these studies will be used to establish the developmental pattern for the composition and organization of MVM and to determine its relationship with the functional capacity of the microvillus surface during development. A secondary objective of this proposal is to study dietary and hormonal regulation of MVM development using the aforementioned parameters. We will determine if the MVM developmental pattern can be modulated by qualitative (breast milk vs. artifical formula diet) and quantitative (volume of milk ingested, duration of weaning period) changes in nutrients or by known growth stimulants (cortisone, thyroxin, epidermal growth factor) during the perinatal period. This research may enhance our knowledge of MVM maturation at the molecular level and provide a better understanding of controlling mucosal host defenses in newborns.